Associations between Deceased-Donor Urine Injury Biomarkers and Kidney Transplant Outcomes

Abstract

Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinaseassociated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean6SD 6-month eGFR was 55.7623.5 ml/min per 1.73 m 2 . In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant.

Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury

“…14,15 Briefly, we collaborated with five organ procurement organizations (OPOs). These OPOs collected donor urine samples as per study protocol at the time of organ procurement between April 2010 and November 2013 from donors whose surrogates had given consent for research.…”

Urinary neutrophil gelatinase-associated lipocalin is a biomarker of delayed graft function after kidney transplantation

“…It has been reported that increased local production of NGAL by the tubular epithelium of DGF kidneys contributes to the high circulating and urine levels, reflecting the ischemia/reperfusion stress applied to the transplanted kidney before organ withdrawal, during the storage period, and during successive reperfusion. [9][10][11] NGAL is a 25 kDa protein belonging to the lipocalin superfamily. It was initially found in activated neutrophils; however, many other cells, like kidney tubular cells, may produce it in response to various insults.…”

Pre-transplant biomarkers and prediction of post-transplant outcomes in kidney transplantation

“…However, failed to predict DGF in the receiver operating characteristic (ROC) analysis. Reese et al (35) also documented the association of donor uNGAL with consequent DGF, but with lower incidence in comparison to the findings of Hollmen et al (34). Furthermore, both uNGAL and uL-FABP were in association with a lower estimated GFR (eGFR) at sixmonths, but only in recipients in absence of DGF.…”

“…Furthermore, both uNGAL and uL-FABP were in association with a lower estimated GFR (eGFR) at sixmonths, but only in recipients in absence of DGF. Based on these data, the authors concluding that donor urine injury biomarkers procure exiguous value to predict DGF and early allograft function after transplantation (35). Koo et al (36) reconsidered these data with their findings.…”